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Diuretics Flashcards

1
Q

What is the primary function of diuretics? What do they treat (generally)?

A

Increase volume of urine

Treats edema

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2
Q

From what drug were the first diuretics all derived?

A

Sulfonilamide

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3
Q

What kinds of conditions can lead NaCl intake to exceed output?

A

CHF or Renal Failure

Leads to edema

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4
Q

About what % of NaCl is reabsorbed in the PCT?

A

65%

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5
Q

About what % of NaCl is reabsorbed in the thin descending limb?

A

0%

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6
Q

About what % of NaCl is reabsorbed in the thick ascending limb?

A

35%

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7
Q

About what % of NaCl is reabsorbed in the DCT?

A

10%

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8
Q

About what % of NaCl is reabsorbed in the collecting duct?

A

2-5%

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9
Q

How do most diuretics get into the luminal fluid? What is the exception?

A

Most reach the luminal fluid by organic acid and base secretion in the PCT. They are not filtered at the glomerulus because they are protein bound.

Mannitol is the exception and it is filtered at the glomerulus.

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10
Q

What transporters are present on the basal side of the PCT epithelium?

A

Na+/K+ ATPase

Na+/HCO3- cotransporter

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11
Q

Acetazolamide

MOA

A

Reversible inhibition of carbonic anhydrase

Inhibits reabsorption of HCO3- in the PCT

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12
Q

Acetazolamide

Adverse Effects

A

Metabolic acidosis (prevents HCO3- reabsorption into blood)

Hypokalemia

Calcium phosphate stones (decrease pH of the luminal fluid)

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13
Q

Acetazolamide

Contraindication

A

Cirrhosis

Increased urine pH leads to less NH3 excretion, therefore giving higher NH3 serum levels

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14
Q

List the four carbonic anhydrase inhibitors

A

Acetazolamide
Dichlorphenamide
Methazolamide
Dorzolamide

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15
Q

Acetazolamide

Clinical Uses

A

Diuretic (pretty weak)

Glaucoma (reduces intraocular pressure)

Urinary alkalinization

Acute mountain sickness (prophylaxis – decrease hemoglobin’s affinity for O2 so more O2 is deposited at tissues)

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16
Q

Mannitol is what kind of diuretic?

Where does mannitol have its major effects?

A

Osmotic Diuretic

Major effects in the PCT, descending limb of loop of Henle, collecting ducts (if ADH present)

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17
Q

How does mannitol reach the luminal fluid?

A

Gets filtered at the glomerulus.

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18
Q

Mannitol

Administration

A

IV only

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19
Q

Mannitol

Adverse Effects

A

Increased plasma osmolality
Moves water out of the cells into the ECF, which can worsen heart failure
Acute pulmonary edema
Dehydration

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20
Q

Mannitol

Clinical Indications

A

Maintain or increase urine volume
Could treat acute renal failure
Reduce intracranial pressure
Reduce intraocular pressure

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21
Q

Mannitol

Contraindications

A

CHF
Chronic Renal failure
Pulmonary edema

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22
Q

What transporter is present on the apical membrane of the thick ascending limb?

A

Na+/K+/Cl- cotransporter

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23
Q

Action of the Na+/K+/Cl- cotransporter helps cause paracellular transport of what substances in the thick ascending limb?

A

Mg2+ and Ca2+

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24
Q

What is the primary mechanism of action for loop diuretics?

A

Inhibit the Na+/K+/Cl- cotransporter

Vasodilation – increase renal blood flow (prostaglandin mediated)

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25
Furosemide | MOA
Inhibit the Na+/K+/Cl- cotransporter Renal vasodilation Decreases reabsorption of Mg2+ and Ca2+
26
Furosemide | Pharmacokinetics
Short half life (1-1.5 hrs)
27
Furosemide | Adverse Effects
``` Hyponatremia Hypokalemia Hypomagnesemia Metabolic alkalosis Ototoxicity ```
28
Furosemide | Clinical Indications
Acute Pulmonary Edema Edema assoc. with CHF Acute hypercalcemia Acute hyperkalemia
29
List the 4 Loop Diuretics
Furosemide Bumetanide Torsemide Ethacrynic Acid
30
Why is ethacrynic acid used as a last resort as a loop diuretic?
It is both nephrotoxic and ototoxic
31
What channel is present on the distal convoluted tubule apical membrane?
Na+/Cl- cotransporter
32
What channel is present on the distal convoluted tubule basolateral membrane? What receptor is present there?
Na+/K+ ATPase Na+/Ca2+ antiporter (brings Na+ into cell and Ca2+ into blood) PTH Receptor is also present on basolateral membrane
33
Hydrochlorothiazide | MOA
Blocks the Na+/Cl- cotransporter on the apical membrane | Allows for more Ca2+ reabsorption
34
Hydrochlorothiazide | Adverse Effects
``` Hyponatremia Hypokalemia Metabolic alkalosis Hyperglycemia Hyperlipidemia Dehydration ```
35
Hydrochlorothiazide | Clinical Uses
HTN CHF Reduce Ca2+ excretion to prevent kidney stones
36
List the thiazide diuretics
``` Hydrochlorothiazide Chlorothiazide Metolazone Indapamide Chlorthalidone ```
37
What channels are present on the apical membrane of principal cells of the collecting ducts?
Na+ channels (moving Na+ into the cell) K+ channels (moving K+ out of the cell and into lumen) H2O channels, bring H2O into cell
38
Aldosterone binds its receptor where? What does that cause?
Binds receptors in principal cells of the collecting ducts. Causes increased transcription of the Na+/K+ ATPase and apical Na+ channels
39
Intercalated Cells contain what apical transporter? What is it regulated by?
H+ ATPase Pumps H+ into the luminal fluid Regulated by aldosterone
40
How do Carbonic anhydrase inhibitors cause hypokalemia?
They cause an increased conc of Na+ and HCO3- to reach the collecting ducts, which leads to a greater negative luminal potential. This forces more K+ out of the cells into the lumen, thus wasting more K+ and causing hypokalemia
41
How do thiazide and loop diuretics cause hypokalemia?
Cause an increased delivery of Na+ and Cl- to the collecting ducts, increasing the negative luminal potential in the collecting ducts and pulling more K+ out into the lumen. Causes hypokalemia (K+ wasting)
42
How do thiazide and loop diuretics cause metabolic alkalosis?
Cause more Na+ and Cl- to reach the collecting ducts, thus increasing the negative luminal potential. Leads to more H+ being pumped out of intercalated cells by the H+ ATPase, thus causing metabolic alkalosis
43
Where in the nephron do K+ sparing diuretics work?
Collectig tubules
44
When should K+ sparing diuretics NEVER be given?
DO NOT use K+ sparing diuretics when hyperkalemia is a risk | DO NOT coadminister with an ACE inhibitor
45
Spironolactone | MOA
Aldosterone receptor antagonist | Anti-androgenic effects
46
Spironolactone | Adverse Effects
``` Hyperkalemia Metabolic acidosis Gynecomastic, amenorrhea, impotence GI Upset CNS effects ```
47
Spironolactone | Clinical Indications
Primary or Secondary Hyperaldosteronism Liver cirrhosis -- DOC HTN
48
Eplerenone | MOA
Aldosterone receptor antagonist Does NOT have the same anti-androgenic effects that spironolactone does, so there are fewer side effects
49
How can spironolactone cause metabolic acidosis?
Blocking aldosterone decreases the negative luminal potential. Leads to less H+ efflux from the intercalated cells, so the H+ accumulates in the blood
50
Amiloride | MOA
Blocks Na+ channels on principal cells K+ sparing diuretic because it decreases driving force for K+ to leave cells
51
Amiloride | Adverse Effects
Hyperkalemia GI upsets Muscle cramps CNS effects
52
Amiloride | Clinical Indications
Edema HTN Usually combined with a loop or thiazide diuretic to prevent K+ loss
53
Triamterene | MOA
Blocks Na+ channels in principal cells K+ sparing diuretic because it decreases driving force for K+ to leave cells
54
``` ADH Antagonists What class of drugs is now used? List them and specify the receptor they antagonize ```
Vaptams V2 receptor antagonists Tolvaptam Mozavaptam Lixivaptam V1a and V2 receptor antagonist Conivaptam
55
ADH Antagonists | Indications
SIADH Euvolemic or hypervolemic hyponatremia CHF
56
ADH Antagonists | Adverse Effects
``` Hypernatremia Thirst Dry mouth Hypotension Dizziness ```
57
What kind of diuretic would you typically give for chronic right heart failure?
Oral Loop diuretic
58
What kind of diuretic would you typically give for acute left heart failure?
IV Loop diuretic | You need aggressive and rapid therapy
59
What is hyponatremia clinically defined as?
Serum Na+ concentration less than 136 mEq/L
60
What kind of hyponatremia may be treated by administration of saline?
Hypovolemic hyponatremia
61
What drugs are used to treat hyponatremia?
ADH receptor antagonists (Vaptams) They increase serum Na+ conc and decrease urine osmolality
62
What kind of diuretic should be used for uncomplicated HTN?
Thiazide diuretic
63
For patients with diabetes and chronic kidney disease, what hypertensive medications should be used?
Two or more antihypertensive meds... | likely including a thiazide diuretic
64
What is nephrogenic diabetes insipidus?
Loss of ADH effectivity in principal cells of the collecting tubules
65
What diuretics should be used to treat nephrogenic diabetes insipidus? Why?
Thiazide diuretics | They may lead to increased Na+ channel synthesis and aquaporin synthesis in principal cells
66
Kidney stones are mostly made of what?
Calcium
67
Which diuretics are useful at preventing kidney stones? Why?
Thiazide diuretics are useful at preventing kidney stones because they increase the reabsorption of Ca2+.
68
Which diuretics have an increased risk of causing kidney stones? Why?
Loop diuretics because they prevent the reabsorption of Ca2+, thus increasing Ca2+ concentration in the lumen of the nephron
69
What diuretics should be used in hypercalcemia?
Loop diuretics (increase excretion of Ca2+)
70
What diuretics should be avoided in hypercalcemia?
Thiazide diuretics (increase reabsorption of Ca2+)

Pharmacology (67 decks)

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